Biology subjects

Bernard, C.

Publications and source records attributed to Bernard, C..

8 recordsLinked to original sources

bioRxiv2018

Subcellular localization of microcystin in the liver and the gonad of medaka fish acutely exposed to microcystin-LR

Among the diverse toxic components produced by cyanobacteria, microcystins (MCs) are one of the most toxic and notorious cyanotoxin groups. Besides their potent hepatotoxicity, MCs have been revealed to induce potential reproductive toxicity in various animal studies. However, little is still known regarding the distribution of MCs in the reproductive organ, which could directly affect reproductive cells. In order to respond to this question, an acute study was conducted in adult medaka fish (model animal) gavaged with 10 {micro}g.g-1 body weight of pure MC-LR. The histological and immunohistochemical examinations reveal an intense distribution of MC-LR within hepatocytes along with a severe liver lesion in the toxin-treated female and male fish. Besides being accumulated in the hepatocytes, MC-LR was also found in the connective tissue of the ovary and the testis, as well as in oocytes and degenerative spermatocyte-like structures. Both liver and gonad play important roles in the reproductive process of oviparous vertebrates. This observation constitutes the first observation of the presence of MC-LR in the reproductive cell of a vertebrate model with in vivo study. Our results, which provide intracellular localization of MC-LR in the gonad, advance our understanding of the potential reproductive toxicity of MC-LR in fish.

cell biology↗

bioRxiv2018

Specific metabolic signatures of fish exposed to cyanobacterial blooms

With the increasing impact of the global warming, occurrences of cyanobacterial blooms in aquatic ecosystems are becoming a main ecological concern around the world. Due to their capacity to produce potential toxic metabolites, interactions between the cyanobacteria/cyanotoxin complex and the other freshwater organisms have been widely studied in the past years. Non-targeted metabolomic analyses have the powerful capacity to study a high number of metabolites at the same time and thus to understand in depth the molecular interactions between various organisms in different environmental scenario and notably during cyanobacterial blooms. In this way during summer 2015, liver metabolomes of two fish species, sampled in peri-urban lakes of the ile-de-France region containing or not high concentrations of cyanobacteria, were studied. The results suggest that similar metabolome changes occur in both fish species exposed to cyanobacterial blooms compared to them not exposed. Metabolites implicated in protein synthesis, protection against ROS, steroid metabolism, cell signaling, energy storage and membrane integrity/stability have shown the most contrasted changes. Furthermore, it seems that metabolomic studies will provide new information and research perspectives in various ecological fields and notably concerning cyanobacteria/fish interactions but also a promising tool for environmental monitoring of water pollutions.

ecology↗

bioRxiv2018

Global metabolomic characterizations of Microcystis spp. highlights clonal diversity in natural bloom-forming populations and expands metabolite structural diversity

Cyanobacteria are photosynthetic prokaryotes that are able to synthetize a wild rang of secondary metabolites exhibiting noticeable bioactivity, comprising toxicity. Microcystis represents one of the most common cyanobacteria taxa constituting the intensive blooms that arise nowadays in freshwater ecosystems worldwide. They produce numerous cyanotoxins (toxic metabolites), which are potentially harmful to Human health and aquatic organisms. In order to better understand the variations in cyanotoxins production between clones of the Microcystis, we investigate the diversity of several strains isolated from the same blooms, from different populations in various geographical area.\n\nTwenty-four clonal strains were compared by genotyping with 16S-ITS fragment sequencing and metabolites chemotyping using LC ESI-qTOF mass spectrometry. While, genotyping can only discriminate between the different species, the global metabolomes reveal clear discriminant molecular profiles between strains. These profiles can be clustered primarily according to their global metabolite content, then to their genotype, and finally to their sampling localities. A global molecular network of all metabolites highlights the production of a wide set of chemically diverse metabolites, comprising only few microcystins, but many aeruginosins, cyanopeptolins and microginins, along with a large set of unknown molecules. They represent the molecular biodiversity that still remain to be investigated and characterized at their structure as well as at their potential bioactivity or toxicity levels.

microbiology↗

bioRxiv2018

Clinical data specification and coding for cross-analyses with omics data in autoimmune disease trials

ObjectivesAutoimmune and inflammatory diseases (AIDs) form a continuum of autoimmune and inflammatory diseases, yet AIDs nosology is based on syndromic classification. The TRANSIMMUNOM trial (NCT02466217) was designed to re-evaluate AIDs nosology through clinic-biological and multi-omics investigations of patients with one of 19 selected AIDs. To allow cross-analyses of clinic-biological data together with omics data, we needed to integrate clinical data in a harmonized database.\n\nMaterials and MethodsWe assembled a clinical expert consortium (CEC) to select relevant clinic-biological features to be collected for all patients and a cohort management team comprising biologists, clinicians and computer scientists to design an electronic case report form (eCRF). The eCRF design and implementation has been done on OpenClinica, an open-source CFR-part 11 compliant electronic data capture system.\n\nResultsThe CEC selected 865 clinical and biological parameters. The CMT selected coded the items using CDISC standards into 5835 coded values organized in 28 structured eCRFs. Examples of such coding are check boxes for clinical investigation, numerical values with units, disease scores as a result of an automated calculations, and coding of possible treatment formulas, doses and dosage regimens per disease.\n\nDiscussion21 CRFs were designed using OpenClinica v3.14 capturing the 5835 coded values per patients. Technical adjustment have been implemented to allow data entry and extraction of this amount of data, rarely achieved in classical eCRFs designs.\n\nConclusionsA multidisciplinary endeavour offers complete and harmonized CRFs for AID clinical investigations that are used in TRANSIMMUNOM and will benefit translational research team.

clinical trials↗

bioRxiv2017

On the difficulty to interpret results when animals are singly housed: experimental epilepsy as a prototypical example

Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.\n\nSignificance StatementMany experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.

neuroscience↗

bioRxiv2017

The circadian hippocampus and its reprogramming in epilepsy: impact for chronotherapeutics

Gene and protein expression displays circadian oscillations in numerous body organs. These oscillations can be disrupted in diseases, thus contributing to the disease pathology. Whether the molecular architecture of cortical brain regions oscillates daily and whether these oscillations are modified in brain disorders is less understood. We identified 1200 daily oscillating transcripts in the hippocampus of control mice. More transcripts (1600) were oscillating in experimental epilepsy, with only one fourth oscillating in both conditions. Proteomics confirmed these results. Metabolic activity and targets of antiepileptic drugs displayed different circadian regulation in control and epilepsy. Hence, the hippocampus, and perhaps other cortical regions, shows a daily remapping of its molecular landscape, which would enable different functioning modes during the night/day cycle. The impact of this remapping in brain pathologies needs to be taken into account not only to study their mechanisms, but also to design drug treatments and time their delivery.

neuroscience↗

bioRxiv2017

Non-cell autonomous Otx2 homeoprotein regulates visual cortex plasticity through Gadd45b

The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and non-plastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription. Intriguingly, a reverse effect was found in the adult, where reducing cortical OTX2 resulted in Gadd45b/g up-regulation. Viral expression of Gadd45b in adult visual cortex directly induced ocular dominance plasticity with concomitant changes in MeCP2 foci within parvalbumin interneurons and in methylation states of several plasticity gene promoters, suggesting epigenetic regulation. This interaction provides a molecular mechanism for OTX2 to trigger critical period plasticity yet suppress adult plasticity.

neuroscience↗

bioRxiv2017

The Virtual Mouse Brain: A Computational Neuroinformatics Platform To Study Whole Mouse Brain Dynamics

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brains structure-function relationship, necessitating the close integration of diverse neuroinformatics fields.\n\nHere we extend the open-source simulation software The Virtual Brain to whole mouse brain network modeling based on individual diffusion Magnetic Resonance Imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease.\n\nThe Virtual Mouse Brain enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

neuroscience↗